Determination of regulatory characteristics of specific gene/promoter elements in normal and disease-stressed myocardial tissue with particular attention to the skeletal alpha actin and myosin heavy chain gene promoters and to hybrid hypoxia responsive/tissue specific promoters. Incorporation of hypoxia responsive promoters into regulated gene therapy vectors for ischaemia heart disease.
Characterisation of the effects of cardiac hypertrophy on the expression of the calcium regulatory molecules SERCA2a and phospholamban. Analysis of the role of phosphodiesterase type 4 isoenzymes and myotonic dystrophy protein kinase in regulating phospholamban phosphorilation status and in modifying cardiac myocyte adaptations to hypertrophy.
Examination of the effects on altered cardiac contractility of exoneous expression of contractile protein isoforms (troponin C fast, troponin T) in cardiac myocytes by means of adenoviral gene transfer into heart cells in culture and the myocardium in vivo.
